Department of Radiology, Huashan Hospital, National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200040, P. R. China.
Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, P. R. China.
Small. 2022 Sep;18(39):e2203031. doi: 10.1002/smll.202203031. Epub 2022 Aug 25.
Transition-metal dyshomeostasis has been identified as a critical pathogenic factor for the aggregates of amyloid-beta (Aβ) peptide, which is associated with the onset and progression of Alzheimer's disease (AD). Excessive transition-metal ions, especially copper ion (Cu ), catalyze the formation of reactive oxygen species (ROS), triggering neuroinflammation and neuronal cell apoptosis. Therefore, developing a robust chelating agent can not only efficiently bind toxic Cu , but also simultaneously scavenge the over-generated ROS that is urgently needed for AD treatment. In this work, a 2D niobium carbide (Nb C) MXene-based nano-chelator is constructed and its performance in suppressing Cu -induced accumulation of aggregated Aβ peptide and acting as a nanozyme (MXenzyme) with powerful antioxidant property to scavenge excess cellular ROS is explored, and the intrinsic mechanism is revealed by computational simulation. Importantly, the benign photothermal effect of Nb C MXenzyme demonstrates the facilitated permeability of the blood-brain barrier under near-infrared laser irradiation, conquering limitations of the most conventional anti-AD therapeutic agents. This work not only demonstrates a favorable strategy for combating AD by engineering Nb C MXenzyme-based neuroprotective nano-chelator, but also paves a distinct insight for extending the biomedical applications of MXenes in treating transition-metal dyshomeostasis-and ROS-mediated central nervous system diseases.
过渡金属稳态失衡已被确定为淀粉样β（Aβ）肽聚集的关键致病因素，与阿尔茨海默病（AD）的发病和进展有关。过量的过渡金属离子，特别是铜离子（Cu ），会催化活性氧物质（ROS）的形成，引发神经炎症和神经元细胞凋亡。因此，开发一种强大的螯合剂不仅可以有效地结合有毒的 Cu ，还可以同时清除 AD 治疗急需的过量生成的 ROS。在这项工作中，构建了一种二维碳化铌（NbC）MXene 基纳米螯合剂，并探索了其抑制 Cu 诱导的聚集 Aβ肽积累的性能，以及作为具有强大抗氧化性能的纳米酶（MXenzyme）来清除过量细胞 ROS 的性能，通过计算模拟揭示了其内在机制。重要的是，NbC MXenzyme 的良性光热效应证明了在近红外激光照射下血脑屏障通透性的增加，克服了大多数传统抗 AD 治疗剂的局限性。这项工作不仅展示了通过工程化 NbC MXenzyme 基神经保护纳米螯合剂来对抗 AD 的有利策略，而且为扩展 MXenes 在治疗过渡金属稳态失衡和 ROS 介导的中枢神经系统疾病中的生物医学应用提供了独特的见解。
